Introduction: Chronic lymphocytic leukemia (CLL) typically occurs in elderly patients and has a highly variable clinical course. It is important to understand the aspects that affect the outcomes of CLL in a real-world setting. Besides biological factors, other socioeconomic and health system factors may influence the clinical course of CLL. Hence, data from the Brazilian Registry of CLL was analyzed to compare clinical and treatment-related characteristics in patients with CLL treated in public or in private institutions in Brazil. Objective: To describe the outcomes of a series of CLL patients followed in public or in private hospitals in Brazil. Methods: The Brazilian Registry of CLL was started in 2004 as a prospective non-interventional data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. For this analysis, we included all patients with minimum available data for analysis of patient and disease characteristics and survival. Results/discussion: From January 2004 to July 2020, 2927 patients from 37 centers met eligibility criteria for this analysis: 2324 (79%) were followed at public hospitals and 603 (21%) at private hospitals. The majority were male (57%), with median age of 65 years (ranging from 23 to 106). Binet stage was A in 1618 (58%) patients, B in 628 (23%) and C in 525 (19%). FISH for del(17p) was performed in only 479 patients (16%), while FISH for the most common aberrations [del(13q), +12, del(11q), and del(17p)] was performed in only 445 patients (15%). IGVH mutational status was performed in only 211 patients (7%), and karyotype in only 140 patients (5%). Comparing public and private hospitals, we observed that patients in public hospital are slightly older (median age 66 years vs. 64 years for private hospitals, P=0.04), had more advanced diseases at diagnosis (frequency of Binet B or C was 44% in public vs. 32% in private hospital, P<0.0001), and there were more patients with elevated creatinine levels (14% vs. 10%, P=0.03). All prognostic markers were significantly more available in private than in public hospitals: FISH for del17p (42% of cases vs. 10%, respectively, P<0.0001), IGVH mutational status (13% vs. 6%, respectively, P<0.0001) and karyotype (16% vs. 2%, respectively, P<0.0001). The frequency of del(17p) was similar between public and private hospitals (10% vs. 11%, P=NS), while the frequency of unmutated IGHV status was more common in private hospitals, although not statistically different (60% vs. 48%, P=0.09). Analyzing 2102 diagnosed after 2010, we observed that 864 patients (41%) were treated after a median time of 7 months (range: 0-267) after diagnosis. First line treatment was predominantly based chlorambucil (45%) or fludarabine (40%). Anti-CD20 monoclonal antibody was used in only 39% of cases: (rituximab in 35% and obinutuzumab in 4%). Novel agents were used in first line in only 2% of patients, and in most cases in the context of a clinical trial. Of note, most patients (86%) with del(17p) detected by FISH were treated with chemoimmunotherapy. When comparing treatments between public or private hospitals we observed striking differences: in public hospitals there were significantly less patients receiving fludarabine-base regimens (36% vs. 54%, P<0.0001), and anti-CD20 monoclonal antibodies (28% vs. 78%, P<0.0001). Overall survival at 6 years was significantly worse in public than in private hospitals (72% vs. 93%, respectively, P<0.0001). After a multivariate analysis, survival in patients from public hospitals remained significantly worse than in private hospitals (hazard ratio 3.4, 95% confidence interval 2.4 - 4.8), after correcting for age, Binet staging and renal function. Conclusion: Our data indicate that are striking differences between patients treated in public or private hospitals in Brazil. The lack of accessibility to basic laboratory tests for prognostic factors and adequate therapies probably explains the worse outcome of patients treated in public institutions. In fact, prognostic testing rates were poor in both contexts and most high-risk patients received chemoimmunotherapy first-line. Urgent strategies are needed to increase accessibility to prognostic testing and to novel agents for quality improvement in health care in CLL patients in Brazil. Disclosures No relevant conflicts of interest to declare.

Introduction: Some patients with CLL will require treatment at diagnosis, but many other will remain untreated under observation for several years. In 2008, the International Workshop on Chronic Lymphocytic Leukemia(IWCLL) defined the criteria for treatment indications, which have been widely used in daily practice and in clinical trials. We have observed that many patients tolerate several of these clinical manifestations without treatment need, especially in public hospitals were resources and treatment options are scarce. We identified 5 reference centers for CLL that share the same profile of being more conservative in indicating treatment for CLL patients. We decided to analyze if more conservative local criteria for treatment indication impacts on patients' outcomes. Objective: To describe the outcomes of a series of CLL patients treated according to locally defined more conservative criteria for initiating treatment. Methods: The Brazilian Registry of CLL was started in 2004 as a prospective observational data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. We retrospectively evaluated all patients with CLL in the Brazilian Registry of CLL who were followed between January 2013 and April 2020 at the 5 reference centers (3 public and 2 private). The following local criteria were used for treatment indications to all patients included: 1) persistent and progressive symptomatic cytopenias (no predefined minimum levels), 2) Massive or symptomatic lymphadenopathy, 3) Massive or symptomatic splenomegaly, 4) Disease-related symptoms, only if persistent and if other causes were excluded, and 5) Autoimmune complications including anemia or thrombocytopenia non-responsive to steroids. Progressive lymphocytosis and extranodal manifestations were not considered for treatment indication. Results: A total of 581 patients were followed during the observation period of 7 years (median follow-up was 40 months (range: 3-86). Median age was 65 years (range: 32-98) and most patients were male (57%). Binet stage was A in 67%, B in 14% and C in 19% of cases. FISH, performed in only 199 patients (34%), was normal in 47%, and showed del13q in 22%, trisomy 12 in 17%, del11q in 8% and del17p in 7%. According to IWCLL criteria, 257 (44%) presented indication for treatment over the time: 140 (55%) at diagnosis and 117 (45%) during follow-up. Based on the local criteria, 148 (25%) patients met criteria for indication of treatment. Therefore, 109 patients with IWCLL indication were not treated to date according to the local criteria. The IWCLL indications for these untreated patients were: cytopenias in 50 patients (48%), constitutional symptoms in 37 patients (35%), progressive lymphocytosis in 9 (9%), and lymphadenopathy or splenomegaly in 8 (8%). The median observation time for these untreated patients from the time of indication of treatment by IWCLL until the analysis was closed was 39 months, ranging from 3 to 86 months. Of the 109 untreated patients, 12 (13%) died during follow-up: 4 from infections probably unrelated to CLL (all patients were elderly, Binet A, non-neutropenic and non-hypoglobulinemic), 2 from cardiac causes, 1 from a car accident and 5 of unknown causes (lost follow-up after at least 2 years). No deaths were attributable to LLC. Overall survival at 4 years was 90% for the patients who were treated versus 89% for the patients who were not treated (P=0.85). Conclusion: Our data suggest that it is feasible and safe to adopt more conservative criteria to indicate treatment in a CLL patient. A more restrict approach may not only reflect in a significant financial impact to the health care system but also avoid premature exposition to prolonged and/or potentially toxic treatments. This finding might be of special interest to low-income countries. Disclosures No relevant conflicts of interest to declare.

5117 Background- Thalidomide (Thal) is a pro-apoptotic, immunoregulatory and antiangiogenic agent for MM. Although it is used since the 90's, the optimal combined treatment remains inconclusive. This is a preliminary analysis of the first Latin American prospective open-label study comparing three different combinations with Thal for MM patients not eligible for autologous SCT. Patients and Methods- Eligible patients were randomized to one of the three arms and received nine 28-days induction cycles. All patients received Thal(100–200mg/d) and one of the following: A- Cyclo (50mg/d)+ Dexa (40mg/D1-4, 15–18 in cycles 1 and 2, D1-4 in cycles 3 to 9), B- Dexa (40mg/D1-4, 9–12, 17–20 in cycles 1,3,5,7 and 9, D1-4 in even cycles) or C- Mel (4mg/m2/7d)+ Pred (40mg/m2/7d). Thereafter, they were randomized to maintenance treatment until progression disease or unacceptable toxicity, as follows: A1-Thal (100mg/d)+Pred (50mg/each other day) or B1-(Thal 100mg/d). All patients received aspirin as thromboprophylaxis and sulpha-trimetroprim as prophylaxis for infection. If indicated, they received biphosphonate monthly for 24 months, and then quarterly. Before study initiation, informed consent was obtained from patients and evaluation was performed at the end of each cycle. The primary endpoint were response rate and response duration. The secondary endpoints were safety, OS and PFS. IMWG index was utilized to analyze response criteria. SPSS 15.0 for windows® were used for statistical analysis. Results- Enrolment started on February 2007, and a total of 60 patients have been included. Median age at randomization was 71 (56–84) years-old, and 52% of patients were female. Durie-Salmon stages were 12% II, 82% III and ISS stages were 47% II and 28% III. Fifty-one per cent of patients presented IgG monoclonal component. There were no significant differences comparing response > VGPR and treatment arms after three, six and nine cycles. However, the PFS is significant when compared CTD/MPT and TD arms (p=0.01). There was no difference in OS. Discussion- This analysis showed that Thal combinations are effective in MM patient treatment. We have not observed different responses between the tree arms. The progression free survival is significant in favor of alkylating combination than thal+dexa (p=0.01). Toxicity was manageable and balanced between the tree different arms. We would like to thank Dr. Jesus San Miguel and Dra. Maria-Victoria Mateos who have collaborated in this study. Disclosures: No relevant conflicts of interest to declare.

5095 Introduction – Multiple myeloma (MM) is a plasma cell dyscrasias characterized by the bone destruction, renal insufficiency, anemia and hypercalcemia. Studies suggest that the disease activity and the degree of angiogenesis in the bone marrow (BM) are related. It has been shown that increased microvessel density (MVD) in MM patients`BM specimens is associated with poor prognosis, and BM MVD at diagnosis is an important prognostic factor for survival of patients. Due to the anti-angiogenic effect, Thal is becoming consolidated as a therapeutic option for the treatment of MM. The presence of cytotoxic CD57+ T lymphocytes in the BM in MM patients who have never been treated correlates with the clinical progression of the patients. The present study has the objective of presenting findings of the anti-angiogenic effect of thalidomide, correlating with the reduction of MVD in the obtained response, as well as verifying the presence of CD57+ lymphocytes before and after the treatment, correlating this with the rate response. Materials and methods– BM were collected from the posterior iliac crest in MM patients who had never been treated at least 12 weeks after having initiated treatment with Thal or up to the fourth week after discontinuing its use. Patients who had previously received Thal were excluded. The bone marrow biopsies were done by two pathologists who were blind as to the disease treatment phase. Angiogenesis was estimated based on the MVD, utilizing the anti-CD34 antibody as an immunohistochemical marker. The slides were photographed at 03 sites of densely concentrated vessels selected by counting under 400X magnification. The final density of the microvessel site median was determined. The CD57+ lymphocyte analysis was made for plasmocyte concentration zones, determining the final count using the median of three sites. Statistical analysis was performed with the SPSS 15.0 for Windows, a t-parametric test for equal averages and Spearman correlation. Results– There was a total of 20 patients (pre- and post-treatment). The median age was 64 (40–82 years), 65% of the cases being male. The Durie-Salmon Staging distribution: IIA/B= 10 % and IIIA/B=90%, and ISS: 2=45% and 3=35%. The IgG isotype was present in 70% of the cases. The therapeutic schedule made use of target doses of thalidomide at 200mg/d. Fourteen patients utilized the Thal and dexamethasone (TD) schedule, four patients, cyclophosphamide+TD (CTD), one patient, Melphalan+prednisone+Thal (MPT) and one patient combination TD+CTD. Eleven patients received a 90-day treatment between collections, seven, a 120-day treatment, one, a 150-day treatment and one, a 270-day treatment. The median MVD count of pre-thal CD34 was 11.42, and post-thal, 7.17 (p=0.01). The pre-thal CD57 median was 26.42 and the post-treatment, 21.58 (not significant). There was a negative post-CD34 versus overall response correlation (p=0.04) and a positive CD57+ versus overall response correlation (p=0.05). Pre-CD34 versus International Staging System correlations (p=0.01) were observed. Another unexpected observation was the analysis of the gender as an independent variable, it was observed that the post-treatment CD57+ was significantly different between the sexes (p=0.008). Conclusion– This study confirms the anti-angiogenic effect of Thal in MM patients, with reduced MVD by CD34 analysis, in addition to its correlation with the overall response. It also demonstrates the significant correlation between the post-treatment CD57+ lymphocytic population and the overall response. The unexpected finding was the significant difference in the quantity of lymphocytes present in the post-treatment BM between the genders (increased in men and reduced in women). Furthermore, it was observed that a greater quantity of MVD correlates with the worst ISS staging. Disclosures: No relevant conflicts of interest to declare.

Chronic lymphocytic leukaemia (CLL) has a highly variable clinical course. In addition to biological factors, socioeconomic factors and health system characteristics may influence CLL outcome. Data from the Brazilian Registry of CLL were analyzed to compareThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.